Northwest-Alaska Pharmacogenomics Research Network “Pharmacogenetics in Rural and Underserved Populations” Kenneth Thummel 1 and Wylie Burke 2 Depts. of Pharmaceutical Sciences 1 and Bioethics & Humanities 2 , University of Washington, Seattle, WA Clinical/Translational Tamoxifen – CYP2D6 Genotype- Pharmacokinetics (PK) Relationship (Aim 2A; UM, SCF, UW) Tacrolimus – CYP3A Genotype-PK Relationship (Aim 2B; UW, SCF, UM) Warfarin – CYP2C9, CYP4F2, VKORC1, GGCX Genotype- Pharmacodynamic Relationships (Aim 2C; SCF, UW) Warfarin – Gene variation penetrance as a function of rural vs. urban INR monitoring (Aim 4A; GHRI, UW) Assessment & Capacity Development Focus groups/consultation with AI/AN community members; health care provider deliberation (Aim 1A; UM, SCF, UAF, UW) Develop infrastructure to track adverse drug reactions in rural NW/Alaska for pharmacogenomic studies (Aim 4B; UW ITHS – WWAMI) Discovery SNP Discovery – CYP2D6, CYP2C9, CYP3A4, CYP3A5, CYP4F2, VKORC1, GGCX (Aim 1B; UM, SCF, UAF, UW) Gene-Diet Interactions/Cell- based systems (Vitamin K, PUFAs) (Aim 3; UAF, UW, PSBC) People in Rural and Urban Washington and Idaho Dual Principal Investigators Ken Thummel, Wylie Burke Program Coordinator Barbara Kavanaugh University of Washington Allan Rettie* Dave Veenstra Dave Blough Helene Starks Rose James Mark Rieder, Melissa Austin, Alfred Berg, Kari Stephens, Connie Davis, Ron Whitener Center for Alaska Native Health Research (CANHR) University of Alaska - Fairbanks Bert Boyer* Scarlett Hopkins Diane O’Brien University of Montana Erica Woodahl* Liz Putnam LeeAnna Muzquiz Mark Pershouse Pat Beatty Resources Gene Resequencing Center Functional Genomics Lab Mass Spectrometry Center Southcentral Foundation Denise Dillard* Douglas Eby Brian Schilling Resources Alaska Stable Isotope Facility CANHR Culture Intervention Core Group Health Research Institute Denise Boudreau* Monica Fujii Puget Sound Blood Center John Kulman* GOALS • To develop collaborative approaches for improving the diversity of populations participating in PGx research , particularly American Indian and Alaska Native people. • To evaluate opportunities for PGx to benefit rural and underserved populations , which traditionally have been understudied, yet may have more to gain clinically and economically from selected PGx applications. * Lead Co-Investigator U01 GM092676